Study: Drug Lowers Blood Pressure in Treatment-Resistant Patients

(Ivanhoe Newswire) — A new drug, darusentan, reduces blood pressure in patients who have not reached treatment goals with three or more conventional antihypertensive drugs.

Professor Michael A Weber, State University of New York, Brooklyn, and colleagues investigated blood-pressure-lowering effects of the new endothelin type A antagonist, darusentan, in patients with treatment-resistant hypertension.

This study represents a new approach to treatment-resistant hypertension by using a class of drugs called endothelin-receptor antagonists. The molecular pathway involving endothelin type A is different from that targeted by conventional blood pressure medications, such as blockers of the renin-angiotensin system, diuretic drugs, and calcium-channel blockers.

This randomized, double-blind study was conducted in 117 sites in North and South America, Europe, New Zealand, and Australia. A total of 379 patients with systolic blood pressure of 140 more, who were receiving at least three blood-pressure-lowering drugs, including a diuretic, at full or maximum tolerated doses, were randomly assigned to 14 weeks’ treatment with placebo or darusentan. Changes in sitting systolic and diastolic blood pressures were measured at baseline and at the end of treatment.

The mean reductions in systolic and diastolic blood pressures were statistically significant with darusentan compared to placebo. The main adverse effects of darusentan were related to fluid accumulation. Edema, or fluid retention, occurred in 27 percent of patients given darusentan, compared with 14 percent given placebo. One patient in the placebo group died of sudden cardiac death, and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.

According to the authors, “Darusentan provided meaningful lowering of systolic and diastolic blood pressures in patients with treatment-resistant hypertension already receiving many well chosen antihypertensive drugs. Generally, darusentan was well tolerated, the main adverse effects being related to fluid retention. The use of this drug accompanied by effective diuretic therapy seems to represent a new and effective strategy for dealing with treatment-resistant hypertension.”

In an accompanying editorial, Dr Bryan Williams Department of Cardiovascular Sciences and NIHR Cardiovascular Biomedical Research Unit, University of Leicester, UK, was quoted as saying that Darusentan offers the potential for a further . . . decrease in systolic blood pressure in people with resistant hypertension, and appears to exert its effects regardless of gender, age, and other concurrent treatments and diseases. But he added: “These findings do not mean that darusentan would necessarily be the best treatment for every patient with resistant hypertension. This important question can only be addressed by further studies directly comparing various existing and newer treatments.” SOURCE: Lancet, September 11, 2009